A comparison of the potential role,of the tetrodotoxin-insensitive sodium channels, PN3/SNS and NaN/SNS2, in rat models of chronic pain
A comparison of the potential role,of the tetrodotoxin-insensitive sodium channels, PN3/SNS and NaN/SNS2, in rat models of chronic pain
复制标题
DOI：
10.1073/pnas.96.14.7640
复制
发表时间：
1999-07-06
影响因子：
11.1
通讯作者：
Hunter, JC
中科院分区：
文献类型：
--
作者：
Porreca, F;Lai, J;Hunter, JC
钠通道表达和功能的改变被认为是外周血淋巴细胞移植后疼痛表现异常的关键分子事件。神经或组织损伤。虽然单个钠通道亚型对这一过程的相对贡献尚不清楚，但至少部分由钠通道PN 3（SNS）介导的河豚毒素抗性电流的生物物理特性表明，它可能在损伤后外周神经元的持续重复放电中发挥专门的病理生理作用。此外，这一假设得到证据的支持，表明选择性“敲低”PN 3蛋白在背根神经节与特定的反义寡脱氧核苷酸：防止痛觉过敏和异常性疼痛引起的慢性神经或组织损伤。与此相反，敲低NaN/SNS 2蛋白，钠通道，可能是第二个可能的候选河豚毒素抗性电流，似乎对神经损伤诱导的行为反应没有影响。这些数据表明，慢性炎症性或神经性疼痛的缓解可能通过选择性阻断或抑制PN 3表达来实现。鉴于PN 3对感觉神经元的分布受限，这种方法可能提供有效的疼痛缓解而没有显著的副作用责任。
Alterations in sodium channel expression and function have been suggested as a key molecular event underlying the abnormal professing of pain after peripheral. nerve or tissue injury. Although the relative contribution of individual sodium channel subtypes to this process is unclear, the biophysical properties of the tetrodotoxin-resistant current, mediated, at least in part, by the sodium channel PN3 (SNS), suggests that it may play a specialized, pathophysiological role in the sustained, repetitive firing of the peripheral neuron after injury. Moreover, this hypothesis is supported by evidence demonstrating that selective "knock-down" of PN3 protein in the dorsal root ganglion with specific antisense oligodeoxynucleotides :prevents hyperalgesia and allodynia caused by either chronic nerve or tissue injury. In contrast, knock-down of NaN/SNS2 protein, a sodium channel that may be a second possible candidate for the tetrodotoxin-resistant current, appears to have no effect on nerve injury-induced behavioral responses. These data suggest that relief from chronic inflammatory or neuropathic pain might be achieved by selective blockade or inhibition of PN3 expression. In light of the restricted distribution of PN3 to sensory neurons, such an approach might offer effective pain relief without a significant side-effect liability.